Abstract
The formation of a hollow lumen in a formerly solid mass of cells is a key developmental process whose dysregulation leads to diseases of the kidney and other organs. Hydrostatic pressure has been proposed to drive lumen expansion, a view that is supported by experiments in the mouse blastocyst. However, lumens formed in other tissues adopt irregular shapes with cell apical faces that are bowed inward, suggesting that pressure may not be the dominant contributor to lumen shape in all cases. Here we use live-cell imaging to study the physical mechanism of lumen formation in Madin-Darby Canine Kidney cell spheroids, a canonical cell-culture model for lumenogenesis. We find that in this system, lumen shape reflects basic geometrical considerations tied to the establishment of apico-basal polarity. A physical model incorporating both cell geometry and intraluminal pressure can account for our observations as well as cases in which pressure plays a dominant role.
Highlights
The formation of a hollow lumen in a formerly solid mass of cells is a key developmental process whose dysregulation leads to diseases of the kidney and other organs
Previous work in Madin-Darby Canine Kidney (MDCK) spheroids and other systems has assumed that lumen growth occurs due to intraluminal hydrostatic pressure[10,11,12,13]
We examined the mechanics of lumen formation and expansion in MDCK cell spheroids, an archetypal cell culture model for studying lumenogenesis
Summary
The formation of a hollow lumen in a formerly solid mass of cells is a key developmental process whose dysregulation leads to diseases of the kidney and other organs. Published images of some model systems, for example MDCK cell spheroids and various in vivo examples of lumens such as liver bile ducts, blood vessels, and pro-amniotic cavities, demonstrate areas of concave lumen curvature, where cell apical faces are bowed into the lumen[1,2,3,5,17,18,19,20,21,22]. These observations suggest that a positive pressure gradient may not be the dominant contributor to the growth of all lumens
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